Although I agree with what has been said in regard to ponatinib, it is as mentioned, a risk benefit issue. A careful medical history may tell you which patients are at risk. The prophylactic suggestions are reasonable and make common sense, but we really have no evidence to prove that these will prevent or reduce the incidence of vascular events. A decision to use ponatinib should be made after carefull review of risk, likely starting at a lower dose as Tim suggests, and very careful monitoring for adverse events. I do disagree somewhat that omacetaxine has a limited role. Although it is technically more difficult to administer, there are positive and durable results in t315i mutations (I have one out now at more than 5 years) and should not be taken off the table as an option. As an allo-transplanter as well, consideration of this as an option if a good donor is available and the patient is healthy, must also remain as a choice. It is still a very viable and effective approach, and should not be reserved for when the patient shows evidence of disease progression. I would identify a donor if available, and if one of the previous drug options is chosen first, even though this can be the next alternative, be prepared to move to this modality sooner rather than later, if they are ineffective or toxic.